title: Immunohistochemical analysis of chromatin remodeler DAXX in high grade urothelial carcinoma.
abstract: OBJECTIVE
  The chromatin remodeler DAXX, a predominantly nuclear protein, regulates the status of chromatin organization. The aim of this exploratory immunohistochemical study was to evaluate DAXX protein expression in high grade invasive urothelial carcinoma (UC) of the bladder as a biological regulator of aggressiveness.
  
  
  METHODS
  Quantitative analysis was made on DAXX immunostained nuclei in tissue sections from 5 cases of bladder normal urothelium (NU) and 5 cases of bladder pT1 UC. Carcinoma in situ (CIS) and high grade papillary carcinoma (HGPCa) were identified in 2 out of 5 UC cases.
  
  
  RESULTS
  The nuclei in UC show an open configuration of the chromatin composed of granules varying in size and distribution and a mean nuclear area 1.7 times greater than that in NU (UC: mean and SD 24.4 ± 11.4 square microns; NU: 14.8 6.5 square microns. The differences are statistically significant). 70% of the NU nuclei are immunostained, whereas 90% of UC nuclei are positive. The mean gray level value in UC, related to the intensity of nuclear immunostaining, is lower than in NU by a factor of 0.94 (UC: mean and SD 100 ± 15; NU: 106 ± 15. The differences are statistically significant). In particular, the value in the nuclei adjacent to the stroma in UC is slightly lower than in the intermediate cell layers by factor of 0.98, whereas in NU it is slightly greater by a factor 1.02 and 1.04 compared to the intermediate and superficial cell layers. The values in CIS and HGPCa are similar to those in UC.
  
  
  CONCLUSIONS
  The quantitative immunohistochemical analysis shows an altered protein expression of chromatin remodeler DAXX in UC and in its preinvasive phases, when compared to NU. DAXX evaluation, if associated with markers related to global DNA methylation and histone acetylation, could be used in clinical practice as a marker of aggressiveness.
  The virtual slides for this article can be found here:http://www.diagnosticpathology.diagnomx.eu/vs/1398457297102379.
authors.affiliation: Section of Pathological Anatomy, Polytechnic University of the Marche Region, School of Medicine, United Hospitals, Via Conca 71, 60126, Torrette Ancona, Italy.
authors.forename: Antonio
authors.initials: A
authors.lastname: Zizzi
authors.forename: Maria Alessandra
authors.initials: MA
authors.lastname: Montironi
authors.forename: Roberta
authors.initials: R
authors.lastname: Mazzucchelli
authors.forename: Marina
authors.initials: M
authors.lastname: Scarpelli
authors.forename: Antonio
authors.initials: A
authors.lastname: Lopez-Beltran
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
authors.forename: Nicola
authors.initials: N
authors.lastname: Paone
authors.forename: Paolo
authors.initials: P
authors.lastname: Castellini
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Montironi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000032:analysis*; D014408:Biomarkers, Tumor / Q000032:analysis*; D002278:Carcinoma in Situ / Q000737:chemistry* / Q000473:pathology; D002291:Carcinoma, Papillary / Q000737:chemistry* / Q000473:pathology; D002467:Cell Nucleus / Q000737:chemistry / Q000473:pathology; D053145:Cell Nucleus Size; D042002:Chromatin Assembly and Disassembly; D056970:Co-Repressor Proteins; D006801:Humans; D007150:Immunohistochemistry; D018832:Molecular Chaperones; D060787:Neoplasm Grading; D009361:Neoplasm Invasiveness; D009687:Nuclear Proteins / Q000032:analysis*; D011237:Predictive Value of Tests; D001749:Urinary Bladder Neoplasms / Q000737:chemistry* / Q000473:pathology; D019459:Urothelium / Q000737:chemistry* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D014408:Biomarkers, Tumor; D056970:Co-Repressor Proteins; C106985:DAXX protein, human; D018832:Molecular Chaperones; D009687:Nuclear Proteins